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GABAC responses were recorded in cultured cone-driven horizontal cells from the catfish retina using the patch clamp technique. At a holding potential of -49 mV, a bicuculline-resistant inward current (IGABA) was observed when 10 microM GABA was applied. The amplitude of IGABA increased as the extracellular Ca2+ ([Ca2+]o) was increased. Concentration-response curves of IGABA at 2.5 and 10 mM -Ca2+-o had similar EC50 (3.0 and 3.1 microM) and Hill coefficients (1.54 and 1. 24). However, the maximal response estimated at 10 mM [Ca2+]o was larger than the maximal response at 2.5 mM [Ca2+]o. Increasing Ca influx through voltage-gated Ca channels and the resulting rise in the intracellular Ca2+ concentration had no effects on IGABA. However, IGABA was inhibited by extracellular divalent cations, with the following order of the inhibitory potency: Zn2+ &gt; Ni2+ &gt; Cd2+ &gt; Co2+. The inhibitory action of Zn2+ on the [Ca2+]o-dependent IGABA increase was noncompetitive. The action of [Ca2+]o on IGABA was mimicked by Ba2+ or Sr2+. These results demonstrate that the extracellular domain of GABAC receptors has two functionally distinct binding sites represented by Ca2+ (facilitation) and Zn2+ (inhibition). Since [Ca2+]o and [Zn2+]o change into the opposite direction by light, it seems likely that they modify cooperatively the efficacy of the positive feedback consisting of the GABAC receptor.

Modulation of GABAC Response by Ca2+ and Other Divalent Cations in Horizontal Cells of the Catfish Retina